title: Metaphyseal fracture healing in a sheep model of low turnover osteoporosis induced by hypothalamic-pituitary disconnection (HPD).
abstract: We recently established a large animal model of osteoporosis in sheep using hypothalamic-pituitary disconnection (HPD). As central regulation is important for bone metabolism, HPD-sheep develop severe osteoporosis because of low bone turnover. In this study we investigated metaphyseal fracture healing in HPD-sheep. To elucidate potential pathomechanisms, we included a treatment group receiving thyroxine T4 and 17β-estradiol. Because clinically osteoporotic fractures often occur in the bone metaphysis, HPD-sheep and healthy controls received an osteotomy in the distal femoral condyle. Half of the HPD-sheep were systemically treated with thyroxine T4 and 17β-estradiol during the healing period. Fracture healing was evaluated after 8 weeks using pQCT, µCT, and histomorphometrical analysis. Bone mineral density (BMD) and bone volume/total volume (BV/TV) were considerably reduced by 30% and 36%, respectively, in the osteotomy gap of the HPD-sheep compared to healthy sheep. Histomorphometry also revealed a decreased amount of newly formed bone (-29%) and some remaining cartilage in the HPD-group, suggesting that HPD disturbed fracture healing. Thyroxine T4 and 17β-estradiol substitution considerably improved bone healing in the HPD-sheep. Our results indicate that fracture healing requires central regulation and that thyroxine T4 and 17β-estradiol contribute to the complex pathomechanisms of delayed metaphyseal bone healing in HPD-sheep.
authors.affiliation: Institute of Orthopaedic Research and Biomechanics, Center of Musculoskeletal Research, University of Ulm, Helmholtzstr. 14, 89081, Ulm, Germany.
authors.forename: Ronny
authors.initials: R
authors.lastname: Bindl
authors.forename: Ralf
authors.initials: R
authors.lastname: Oheim
authors.forename: Pia
authors.initials: P
authors.lastname: Pogoda
authors.forename: Frank Timo
authors.initials: FT
authors.lastname: Beil
authors.forename: Katharina
authors.initials: K
authors.lastname: Gruchenberg
authors.forename: Sandra
authors.initials: S
authors.lastname: Reitmaier
authors.forename: Tim
authors.initials: T
authors.lastname: Wehner
authors.forename: Enrico
authors.initials: E
authors.lastname: Calcia
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Lutz
authors.initials: L
authors.lastname: Claes
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.forename: Anita
authors.initials: A
authors.lastname: Ignatius
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004958:Estradiol / Q000627:therapeutic use; D017102:Fracture Healing / Q000187:drug effects; D007031:Hypothalamus / Q000502:physiology*; D058866:Osteoporotic Fractures / Q000188:drug therapy / Q000503:physiopathology*; D010902:Pituitary Gland / Q000502:physiology*; D012756:Sheep; D013974:Thyroxine / Q000627:therapeutic use
chemical_list: D004958:Estradiol; D013974:Thyroxine
keywords: central control; hypothalamic-pituitary disconnection (HPD); low turnover; metaphyseal fracture healing; osteoporosis